Regulation of endothelin-1 production by a thromboxane A2 mimetic in rat heart smooth muscle cells.

Regulation of endothelin-1 production by a thromboxane A2 mimetic in rat heart smooth muscle cells.
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大鼠心脏平滑肌细胞中血栓素 A2 模拟物对内皮素 1 产生的调节。

DOI:
10.1016/0167-4889(96)00042-0
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发表时间:
1996
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Chua,BH
Chua,BH
中科院分区:
--
文献类型:
--
作者:
Chua,CC;Hamdy,RC;Chua,BH

文献摘要

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Thromboxane A2(TXA2) and ET-1 have been known to play important roles in modulating vascular contraction and growth. The present study was undertaken to examine the effect of TXA2on the induction of endothelin-1 (ET-1) mRNA and protein levels in smooth muscle cells derived from rat heart. U-46619, a stable TXA2mimetic, superinduced preproET-1 mRNA in the presence of cycloheximide in these cells. This effect could be blocked by SQ-29548, a TXA2/prostaglandin H2receptor antagonist and by actinomycin D, an RNA synthesis inhibitor. In addition, H7, a protein kinase C inhibitor, could abolish the induction. Transient transfection experiment revealed that the elevated ET-1 mRNA level after U-46619 treatment was a result of the activation of ET-1 gene activity. The elevated ET-1 message level was accompanied by increased ET-1 release into the cultured medium. These results show that the short-lived TXA2can induce potent and long-lived ET-1. These findings support a potential role for ET-1 in the pathogenesis of coronary atherosclerosis and hypertension evoked by TXA2.